There has been an emerging paradigm shift from the belief that coronary heart disease (CHD) has a purely hereditary/nutritional etiology to the view that CHD may have an infectious etiology. Among the organisms that are suspected to be involved in CHD are pathogens associated with periodontal diseases. Our hypothesis is that invasion of the cells of the arterial wall by certain oral bacteria could represent the injury that either initiates and/or exacerbates the fibroproliferative response of CHD. Thus the aim of this research is to investigate the possible molecular mechanisms involved in the interactions between periodontal pathogens and cardiovascular (CV) tissues with a focus on invasion of the cells of the arterial wall. We have established that strains of Porphyromonas gingivalis and Prevotella intermedia invade both human coronary artery endothelial cells (HCAEC) and coronary artery smooth muscle cells (CASMC). This application is designed to characterize the invasion of the HCAEC. The specific aims include: 1) Determine the mechanism of cell invasion, 2) Determine the effects of P. gingivalis invasion on cardiovascular cells, 3) Use a reporter gene system (IVET) to identify and isolate genes of P. gingivalis involved in cell invasion, 4) Characterize the reporter gene-labeled invasion gene products, and 5) Construct isogenic mutants of each of the putative invasion genes and test the isogenic strains in invasion assays.